Improved neurodevelopmental prognostication in isolated corpus callosal agenesis: fetal magnetic resonance imaging-based scoring system.

OBJECTIVES: Corpus callosal agenesis (CCA) is one of the most common brain malformations and is generally associated with a good outcome when isolated. However, up to 25% of patients are at risk of neurodevelopmental delay, which currently available clinical and imaging parameters are inadequate to predict. The objectives of this study were to apply and validate a fetal magnetic resonance imaging (MRI) anatomical scoring system in a cohort of fetuses with isolated CCA and to evaluate the correlation with postnatal neurodevelopmental outcome. METHODS: This was a retrospective cohort study of cases of prenatally diagnosed isolated CCA (as determined on ultrasound and MRI), with normal karyotype and with known postnatal neurodevelopmental outcome assessed by standardized testing. A fetal brain MRI anatomical scoring system based on seven categories (gyration, opercularization, temporal lobe symmetry, lamination, hippocampal position, basal ganglia and ventricular size) was developed and applied to the cohort; a total score of 0-11 points could be given, with a score of 0 representing normal anatomy. Images were scored independently by two neuroradiologists blinded to the outcome. For the purpose of assessing the correlation between fetal MRI score and neurodevelopmental outcome, neurodevelopmental test results were scored as follows: 0, 'below average' (poor outcome); 1, 'average'; and 2, 'above average' (good outcome). Spearman's rank coefficient was used to assess correlation, and inter-rater agreement in the assessment of fetal MRI score was calculated. RESULTS: Twenty-one children (nine females (42.9%)) fulfilled the inclusion criteria. Thirty-seven fetal MRI examinations were evaluated. Mean gestational age was 28.3 ± 4.7 weeks (range, 20-38 weeks). All fetuses were delivered after 35 weeks' gestation with no perinatal complications. Fetal MRI scores ranged from 0 to 6 points, with a median of 3 points. Inter-rater agreement in fetal MRI score assessment was excellent (intraclass correlation coefficient, 0.959 (95% CI, 0.921-0.979)). Neurodevelopmental evaluation was performed on average at 2.6 ± 1.46 years (range, 0.5-5.8 years). There was a significant negative correlation between fetal MRI score and neurodevelopmental outcome score in the three areas tested: cognitive (ρ = -0.559, P < 0.0001); motor (ρ = -0.414, P = 0.012) and language (ρ = -0.565, P < 0.0001) skills. Using fetal MRI score cut-offs of ≤ 3 (good outcome) and ≥ 4 points (high risk for poor outcome), the correct prognosis could be determined in 20/21 (95.2% (95% CI, 77.3-99.2%)) cases. CONCLUSION: By assessing structural features of the fetal brain on MRI, it may be possible to better stratify prenatally the risk of poor neurodevelopmental outcome in CCA patients. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Normal human brainstem development in vivo: a quantitative fetal MRI study.

OBJECTIVES: To characterize spatiotemporal growth differences of prenatal brainstem substructures and cerebellum, using linear biometry and planimetry on fetal magnetic resonance imaging (MRI). METHODS: In this retrospective study, we included fetuses with normal brain and a precise midsagittal T2-weighted brain MRI sequence obtained between May 2003 and April 2019. The cross-sectional area, rostrocaudal diameter and anteroposterior diameter of the midbrain, pons (basis pontis and pontine tegmentum), medulla oblongata and cerebellar vermis, as well as the transverse cerebellar diameter, were quantified by a single observer. The diameters were also assessed by a second observer to test inter-rater variability. RESULTS: We included 161 fetuses with normal brain and a precise midsagittal MRI sequence, examined at a mean ± SD gestational age of 25.7 ± 5.4 (range, 14 + 0 to 39 + 2) weeks. All substructures of the fetal brainstem and the cerebellum could be measured consistently (mean ± SD interobserver intraclass correlation coefficient, 0.933 ± 0.065). We provide reference data for diameters and areas of the brainstem and cerebellum in the second and third trimesters. There was a significant quadratic relationship between vermian area and gestational age, and all other measured parameters showed a significant linear growth pattern within the observed period (P < 0.001). A significant change in the relative proportions of the brainstem substructures occurred between the beginning of the second trimester and the end of the third trimester, with an increase in the area of the pons (P < 0.001) and a decrease in that of the midbrain (P < 0.001), relative to the total brainstem area. CONCLUSIONS: The substructures of the fetal brainstem follow a distinct spatiotemporal growth pattern, characterized by a relative increase in the pons and decrease in the midbrain, between 15 and 40 weeks of gestation. Caution is needed when interpreting fetal brainstem appearance during the early second trimester, as the brainstem proportions differ significantly from the adult morphology. The reference data provided herein should help to increase diagnostic accuracy in detecting disorders of defective hindbrain segmentation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Quantitative fetal magnetic resonance imaging assessment of cystic posterior fossa malformations.

OBJECTIVE: Normal cognitive development usually requires a structurally intact and complete cerebellar vermis. The aim of this study was to evaluate whether quantification by fetal magnetic resonance imaging (MRI) of vermis- and brainstem-specific imaging markers improves the definition of cystic posterior fossa malformations (cPFM). METHODS: Fetuses diagnosed with cPFM that had an available midsagittal plane on T2-weighted MRI were identified retrospectively and compared with gestational-age (GA) matched brain-normal controls. Fetuses with cPFM were assigned to three groups, according to standard criteria (vermian size and brainstem-vermis (BV) angle): normal vermian area and BV angle < 25° (Group 1); reduced vermian area and/or BV angle of 25-45° (Group 2); and reduced vermian area and BV angle > 45° (Group 3; Dandy-Walker malformation (DWM) group). The number of differentiable vermian lobules and the areas of the vermis, mesencephalon, pons and medulla oblongata were quantified, correlated with and controlled for GA, and compared between the study groups. RESULTS: In total, 142 cases of cPFM were included, with a mean GA of 25.20 ± 5.11 weeks. Cases comprised Blake's pouch cyst (n = 46), arachnoid cyst (n = 12), inferior vermian hypoplasia (n = 5), megacisterna magna (n = 35) and classic DWM (n = 44). In the control group, 148 fetuses were included, with a mean GA of 25.26 ± 4.12 weeks. All quantified areas and the number of differentiable vermian lobules had a significant positive correlation with GA. The number of vermian lobules and the areas of all quantified regions, except for that of the medulla oblongata, differed significantly between the study groups (P ≤ 0.015 for all). The control group had the highest number of differentiable vermian lobules and the DWM group had the lowest (P < 0.01). CONCLUSIONS: Prenatal MRI assessment of vermian lobules is a useful addition to standard neuroradiological and neurosonographic techniques. The quantification of vermian lobules using fetal MRI allows further differentiation of cPFM into subgroups and thereby improves the classification of hindbrain malformations. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal assessment of cerebellar vermian lobulation: fetal MRI with 3-Tesla postmortem validation.

OBJECTIVES: To optimize the imaging assessment of fetal hindbrain malformations, this observational magnetic resonance imaging (MRI) study aimed to assess whether fetal vermian lobulation can be quantified accurately and whether the relative growth of vermian lobules is uniform. METHODS: This retrospective study included singleton fetuses which underwent T2-weighted MRI in vivo with a 1.5-Tesla (T) scanner or within 24 h postmortem with a 3-T scanner between January 2007 and November 2016 at the Medical University of Vienna. We included only those showing normal structural brain development on ultrasound and MRI and which had image quality appropriate for quantitative analysis, i.e. good image quality and a precise midsagittal slice. Fetal brains were segmented and, for all discernible vermian lobules, we determined the mean relative area contribution (MRAC, the proportion of the lobule relative to the total vermian area, in terms of number of voxels). Inter- and intrarater measurement variability of a representative selection (21 cases) was determined by intraclass correlation coefficient (ICC) for voxel-based differences. A linear regression model was used to assess the correlation between the relative size of each vermian lobule (i.e. MRAC) and gestational age. RESULTS: A total of 78 fetuses scanned in vivo aged 18-32 gestational weeks and seven fetuses scanned postmortem aged 16-30 weeks had a precise midsagittal slice and image quality sufficient for quantitative analysis. After 22 weeks of gestation, seven of the nine known vermian lobules could be discriminated reliably. The MRAC showed a mean ± SD difference of only 2.89 ± 3.01% between in-vivo and postmortem measurements. The ICC of voxel-based interrater differences was mean ± SD, 0.91 ± 0.05 and the intrarater ICC was 0.95 ± 0.03. Growth of cerebellar lobules was non-uniform: the MRAC of culmen and DFT (declive + folium + tuber) increased with gestational age, whereas that of lingula, centralis, pyramis and nodulus decreased. The growth of the uvula showed no significant correlation with gestational age. CONCLUSIONS: Fetal vermian lobulation can be assessed accurately and reliably after 22 weeks on precise midsagittal sequences with 1.5-T T2-weighted MRI. Fetal vermian lobules show non-uniform growth, with expansion of DFT and culmen at the expense of the other vermian lobules. Evaluation and elucidation of vermian lobulation in normal fetuses should enable better characterization of fetuses with hindbrain malformations. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Synthetic MR Imaging-Based WM Signal Suppression Identifies Neonatal Brainstem Pathways in Vivo.

BACKGROUND AND PURPOSE: Multidynamic multiecho sequence-based imaging enables investigators to reconstruct multiple MR imaging contrasts on the basis of a single scan. This study investigated the feasibility of synthetic MRI-based WM signal suppression (syWMSS), a synthetic inversion recovery approach in which a short TI suppresses myelin-related signals, for the identification of early myelinating brainstem pathways. MATERIALS AND METHODS: Thirty-one cases of neonatal MR imaging, which included multidynamic multiecho data and conventionally acquired T1- and T2-weighted sequences, were analyzed. The multidynamic multiecho postprocessing software SyMRI was used to generate syWMSS data (TR/TE/TI = 3000/5/410 ms). Two raters discriminated early myelinating brainstem pathways (decussation of the superior cerebellar peduncle, medial lemniscus, central tegmental tract, and medial longitudinal fascicle [the latter 3 assessed at the level of the pons]) on syWMSS data and reference standard contrasts. RESULTS: On the basis of syWMSS data, the decussation of the superior cerebellar peduncle (31/31); left/right medial lemniscus (31/31; 30/31); left/right central tegmental tract (19/31; 20/31); and left/right medial longitudinal fascicle (30/31) were reliably identified by both raters. On the basis of T1-weighted contrasts, the decussation of the superior cerebellar peduncle (14/31); left/right medial lemniscus (22/31; 16/31); left/right central tegmental tract (1/31); and left/right medial longitudinal fascicle (9/31; 8/31) were reliably identified by both raters. On the basis of T2-weighted contrasts, the decussation of the superior cerebellar peduncle (28/31); left/right medial lemniscus (16/31; 12/31); left/right central tegmental tract (23/31; 18/31); and left/right medial longitudinal fascicle (15/31; 14/31) were reliably identified by both raters. CONCLUSIONS: syWMSS data provide a feasible imaging technique with which to study early myelinating brainstem pathways. MR imaging approaches that use myelin signal suppression contribute to a more sensitive assessment of myelination patterns at early stages of cerebral development.

Different from the Beginning: WM Maturity of Female and Male Extremely Preterm Neonates-A Quantitative MRI Study.

BACKGROUND AND PURPOSE: Former preterm born males are at higher risk for neurodevelopmental disabilities compared with female infants born at the same gestational age. This retrospective study investigated sex-related differences in the maturity of early myelinating brain regions in infants born <28 weeks' gestational age using diffusion tensor- and relaxometry-based MR imaging. MATERIALS AND METHODS: Quantitative MR imaging sequence acquisitions were analyzed in a sample of 35 extremely preterm neonates imaged at term-equivalent ages. Quantitative MR imaging metrics (fractional anisotropy; ADC [10-3mm2/s]; and T1-/T2-relaxation times [ms]) of the medulla oblongata, pontine tegmentum, midbrain, and the right/left posterior limbs of the internal capsule were determined on diffusion tensor- and multidynamic, multiecho sequence-based imaging data. ANCOVA and a paired t test were used to compare female and male infants and to detect hemispheric developmental asymmetries. RESULTS: Seventeen female (mean gestational age at birth: 26 + 0 [SD, 1 + 4] weeks+days) and 18 male (mean gestational age at birth: 26 + 1 [SD, 1 + 3] weeks+days) infants were enrolled in this study. Significant differences were observed in the T2-relaxation time (P = .014) of the pontine tegmentum, T1-relaxation time (P = .011)/T2-relaxation time (P = .024) of the midbrain, and T1-relaxation time (P = .032) of the left posterior limb of the internal capsule. In both sexes, fractional anisotropy (P [♀] < .001/P [♂] < .001) and ADC (P [♀] = .017/P [♂] = .028) differed significantly between the right and left posterior limbs of the internal capsule. CONCLUSIONS: The combined use of various quantitative MR imaging metrics detects sex-related and interhemispheric differences of WM maturity. The brainstem and the left posterior limb of the internal capsule of male preterm neonates are more immature compared with those of female infants at term-equivalent ages. Sex differences in WM maturation need further attention for the personalization of neonatal brain imaging.

Impact of Prematurity on the Tissue Properties of the Neonatal Brain Stem: A Quantitative MR Approach.

BACKGROUND AND PURPOSE: Preterm birth interferes with regular brain development. The aim of this study was to investigate the impact of prematurity on the physical tissue properties of the neonatal brain stem using a quantitative MR imaging approach. MATERIALS AND METHODS: A total of 55 neonates (extremely preterm [n = 30]: <28 + 0 weeks gestational age; preterm [n = 10]: 28 + 0-36 + 6 weeks gestational age; term [n = 15]: ≥37 + 0 weeks gestational age) were included in this retrospective study. In most cases, imaging was performed at approximately term-equivalent age using a standard MR protocol. MR data postprocessing software SyMRI was used to perform multidynamic multiecho sequence (acquisition time: 5 minutes, 24 seconds)-based MR postprocessing to determine T1 relaxation time, T2 relaxation time, and proton density. Mixed-model ANCOVA (covariate: gestational age at MR imaging) and the post hoc Bonferroni test were used to compare the groups. RESULTS: There were significant differences between premature and term infants for T1 relaxation time (midbrain: P < .001; pons: P < .001; basis pontis: P = .005; tegmentum pontis: P < .001; medulla oblongata: P < .001), T2 relaxation time (midbrain: P < .001; tegmentum pontis: P < .001), and proton density (tegmentum pontis: P = .004). The post hoc Bonferroni test revealed that T1 relaxation time/T2 relaxation time in the midbrain differed significantly between extremely preterm and preterm (T1 relaxation time: P < .001/T2 relaxation time: P = .02), extremely preterm and term (T1 relaxation time/T2 relaxation time: P < .001), and preterm and term infants (T1 relaxation time: P < .001/T2 relaxation time: P = .006). CONCLUSIONS: Quantitative MR parameters allow preterm and term neonates to be differentiated. T1 and T2 relaxation time metrics of the midbrain allow differentiation between the different stages of prematurity. SyMRI allows for a quantitative assessment of incomplete brain maturation by providing tissue-specific properties while not exceeding a clinically acceptable imaging time.

Comparison of the colon with T1 breath-hold vs T1 free-breathing-A retrospective fetal MRI study.

OBJECTIVES: Fetal magnetic resonance imaging (MRI) plays an increasingly important role in the prenatal diagnosis of gastrointestinal abnormalities. During gestation, the bowel develops T1-weighted hyperintensity due to meconium formation. Currently used T1-weighted sequences are performed in maternal breath-hold (BH) technique, which may take up to 20 s. The free-breathing (FB) T1-weighted 3D radial VIBE (volumetric interpolated breath-hold examination) sequence requires no breath-hold, improving patient comfort. This study aimed to address how well the FB acquisition technique can visualize large bowel structures compared to the routinely performed breath-hold sequence. METHODS: Forty-seven fetal MRI studies between 21 and 36 weeks of gestation without abdominal pathologies on prenatal MRI and ultrasound were included. All fetal scans were performed using a Philips Ingenia 1.5 T MRI. Coronal T1-weighted BH and FB sequences without fat suppression were compared. The following acquisition parameters were used (T1, FB): resolution 1.137 mm, 1.004 mm; matrix size 288 × 288, 448 × 448; FOV 328 mm, 450 mm; TR 81-132 ms, 3.47 ms; TE 4.6 ms, 1.47 ms. Due to the necessity of the breath-hold the duration of the sequence could not exceed 20 s (mean duration of the T1-weighted BH sequence 15.17 s, and mean duration of the FB sequence 26.42 s). In all examined fetuses the following structures were evaluated with respect to their visibility (0-not visible, 1-partially visible, 2-clearly visible): rectum, sigmoid, descending, transverse and ascending colon, cecum. Furthermore, motion artifacts were assessed (0-none, 1-intermediate, 2-severe motion artifacts), and the signal intensity (SI) ratio between maternal fat and fetal rectum SI was calculated. RESULTS: No significant differences in the visibility of sigmoid and colon between BH and FB were detected, only the cecum could be seen slightly better (in 29.8 % of cases) using BH technique. Motion artifacts were similar between BH and FB. There was a non-significant SI difference (p = 0.68) in the rectum, with a higher SI in the BH sequence. CONCLUSIONS: The FB acquisition technique compared to T1 using BH is equal regarding visibility of bowel structures and artifacts. Due to non-inferiority to the BH technique, the FB sequence is a good alternative in cases where BH cannot be performed. As the FB sequence further allows for thinner slices with a good signal, even small bowel loops may be visualized.

Mapping Human Fetal Brain Maturation In Vivo Using Quantitative MRI.

BACKGROUND AND PURPOSE: On the basis of a single multidynamic multiecho sequence acquisition, SyMRI generates a variety of quantitative image data that can characterize tissue-specific properties. The aim of this retrospective study was to evaluate the feasibility of SyMRI for the qualitative and quantitative assessment of fetal brain maturation. MATERIALS AND METHODS: In 52 fetuses, multidynamic multiecho sequence acquisitions were available. SyMRI was used to perform multidynamic multiecho-based postprocessing. Fetal brain maturity was scored qualitatively on the basis of SyMRI-generated MR imaging data. The results were compared with conventionally acquired T1-weighted/T2-weighted contrasts as a standard of reference. Myelin-related changes in T1-/T2-relaxation time/relaxation rate, proton density, and MR imaging signal intensity of the developing fetal brain stem were measured. A Pearson correlation analysis was used to detect correlations between the following: 1) the gestational age at MR imaging and the fetal brain maturity score, and 2) the gestational age at MR imaging and the quantitative measurements. RESULTS: SyMRI provided images of sufficient quality in 12/52 (23.08%) (range, 23 + 6-34 + 0) fetal multidynamic multiecho sequence acquisitions. The fetal brain maturity score positively correlated with gestational age at MR imaging (SyMRI: r = 0.915, P < .001/standard of reference: r = 0.966, P < .001). Myelination-related changes in the T2 relaxation time/T2 relaxation rate of the medulla oblongata significantly correlated with gestational age at MR imaging (T2-relaxation time: r = -0.739, P = .006/T2-relaxation rate: r = 0.790, P = .002). CONCLUSIONS: Fetal motion limits the applicability of multidynamic multiecho-based postprocessing. However, SyMRI-generated image data of sufficient quality enable the qualitative assessment of maturity-related changes of the fetal brain. In addition, quantitative T2 relaxation time/T2 relaxation rate mapping characterizes myelin-related changes of the brain stem prenatally. This approach, if successful, opens novel possibilities for the evaluation of structural and biochemical aspects of fetal brain maturation.